The ATGL Gene Is Associated With Free Fatty Acids, Triglycerides, and Type 2 Diabetes
- Veit Schoenborn1,
- Iris M. Heid23,
- Caren Vollmert2,
- Arno Lingenhel1,
- Ted D. Adams4,
- Paul N. Hopkins4,
- Thomas Illig2,
- Robert Zimmermann5,
- Rudolf Zechner5,
- Steven C. Hunt4 and
- Florian Kronenberg1
- 1Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
- 2GSF-National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany
- 3Institute of Biostatistics and Epidemiology, Ludwig-Maximilian-Universität München, Munich, Germany
- 4Department of Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, Utah
- 5Institute of Molecular Biosciences, Karl-Franzens-University, Graz, Austria
- Address correspondence and reprint requests to Florian Kronenberg, MD, Division of Genetic Epidemiology, Department of Medical Genetics, MolecularClinical Pharmacology, Innsbruck Medical University, Schöpfstr. 41, A-6020 Innsbruck, Austria. E-mail: florian.kronenberg{at}i-med.ac.at
Abstract
Adipose triglyceride lipase (ATGL) was recently described to predominantly perform the initial step in triglyceride hydrolysis and therefore seems to play a pivotal role in the lipolytic catabolism of stored fat in adipose tissue. In the first study investigating genetic variations within the ATGL gene in humans, 12 polymorphisms identified via sequencing and database search were studied in 2,434 individuals of European ancestry from Utah. These polymorphisms and their haplotypes were analyzed in subjects not taking diabetes medication for association with plasma free fatty acids (FFAs) as primary analysis, as well as triglycerides and glucose as a secondary analysis (n = 1,701, 2,193, or 2,190, respectively). Furthermore, type 2 diabetes (n = 342 of 2,434) was analyzed as an outcome. FFA concentrations were significantly associated with several single nucleotide polymorphisms (SNPs) of ATGL (P values from 0.015 to 0.00003), consistent with additive inheritance. The pattern was similar when considering triglyceride concentrations. Furthermore, two SNPs showed associations with glucose levels (P < 0.00001) and risk of type 2 diabetes (P < 0.05). Haplotype analysis supported and extended the shown SNP association analyses. These results complement previous findings of functional studies in mammals and elucidate a potential role of ATGL in pathways involved in components of the metabolic syndrome.
Footnotes
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V.S., I.M.H., and C.V. contributed equally to this article.
Additional information on this article can be found in an online appendix available at http://diabetes.diabetesjournals.org.
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- Accepted January 30, 2006.
- Received November 15, 2005.
- DIABETES
